The
insulin/IGF system plays an important role in
cancer progression. Accordingly, elevated levels of circulating
insulin have been associated with an increased
cancer risk as well as with aggressive and metastatic
cancer phenotypes. Numerous studies have documented that
estrogens cooperate with the
insulin/IGF system in multiple pathophysiological conditions. The biological responses to
estrogens are mainly mediated by the
estrogen receptors (ER)α and ERβ, which act as
transcription factors; however, several studies have recently demonstrated that a member of the
G protein-coupled receptors, named GPR30/
G-protein estrogen receptor (GPER), is also involved in the
estrogen signaling in normal and malignant cells as well as in cancer-associated fibroblasts (CAFs). In this regard, novel mechanisms linking the action of
estrogens through GPER with the
insulin/IGF system have been recently demonstrated. This review recapitulates the relevant aspects of this functional cross-talk between the
insulin/IGF and the estrogenic GPER transduction pathways, which occurs in various cell types and may account for
cancer progression.